Posterior pituitary

Question 1

oxytocin: uterus

Answer 1

-Stimulates contraction of the smooth muscle cells of the uterus
-prevents hemorrhage during birth
-Uterine sensitivity increases throughout pregnancy
-Plasma levels do not increase sharply during parturition
-Role of oxytocin in the initiation of labor is unclear
-given during birth

Question 2

oxytocin: breast

Answer 2

-Myoepithelial cells
-Suckling stimulates the production of oxytocin
-Cells surround the alveoli of the mammary gland → contraction causes milk to move from the alveoli to large sinuses for ejection
-Letdown reflex- 3rd trimester, release of milk, breast are enlarged,

Question 3

ADH

Answer 3

-action- water conservation by increasing the permeability of the distal tubular epithelium to water
-At high concentrations - also causes vasoconstriction
-Plays an important role in maintaining fluid homeostasis and vascular and cellular hydration

Question 4

ADH stimulation and inhibition

Answer 4

-main stimulus for ADH release -> Increased osmotic pressure of water in the body*!
-other major stimulus is:
-Volume depletion
-Sensed by baroreceptors in the left atrium, pulmonary veins, carotid sinus, and aortic arch
-Transmitted to the CNS through the vagus and glossopharyngeal nerves

-Other stimulants for ADH release include:
-Pain, stress, emesis, hypoxia, exercise, hypoglycemia, cholinergic agonists, β-blockers, angiotensin, and prostaglandins

-Inhibitors of ADH release include alcohol, α-blockers, and glucocorticoids

Question 5

lack of ADH and causes

Answer 5

-Central diabetes insipidus [CDI]
-Deficiency of ADH due to a hypothalamic-pituitary disorder
-Primary
-Secondary

-Inability of kidney (distal tubule) to respond normally to ADH -> Causes Nephrogenic Diabetes Insipidus [NDI]

-Vasopressinase-induced DI- breakdown of ADH

-Removal of the pituitary gland usually does not result in permanent diabetes insipidus because some of the remaining hypothalamic neurons produce small amounts of ADH

Question 6

diabetes insipidus pathology and diff dx

Answer 6

-Hypothalamic nuclei and part of the neurohypophyseal tract need to be intact
-Pathology of CDI: always involves the supraoptic and paraventricular nuclei of the hypothalamus or a major portion of the pituitary stalk
-Differential for polyuria:
-CDI
-NDI
-Or compulsive or habitual water drinking (psychogenic polydipsia)
-DM

Question 7

diabetes insipidus (DI)

Answer 7

-Polyuria
-Polydipsia

-Diagnosis:
-Water deprivation test
-Failure to maximally concentrate urine
-ADH levels and response to exogenous ADH help distinguish CDI from NDI
-NDI- no change after giving ADH
-CDI- changes after giving ADH

-Treatment is with intranasal desmopressin or lypressin
-Nonhormonal treatment includes use of diuretics (mainly thiazides)
-ADH-releasing drugs, such as chlorpropamide

Question 8

primary central diabetes insipidus

Answer 8

-Marked decrease in the hypothalamic nuclei of the neurohypophyseal system
Genetic abnormalities of the ADH gene on chromosome 20
Idiopathic

Question 9

secondary (acquired) central diabetes insipidus

Answer 9

-Various lesions:
-Hypophysectomy
-Cranial injuries (particularly basal skull fractures)
-Suprasellar & intrasellar tumors (primary or metastatic)

-Granulomas (sarcoidosis or TB),
-Vascular lesions (aneurysm and thrombosis)
-Infections (encephalitis or meningitis)

Question 10

symptoms and signs of DI

Answer 10

-Onset insidious or abrupt
-Occurring at any age
-Primary CDI: only symptoms are polydipsia & polyuria
-Secondary CDI- S&S of the associated lesions as well!!
-Large quantities of fluid - ingested

-Large volumes (3 to 30 L/day) of dilute urine excreted
-Sp.gr. usually < 1.005 (nml 1.030)
-Osmolality < 200 mOsm/L (nml 280-285mOsm/L)

-Nocturia almost always occurs -> does not occur with psychogenic polydipsia
-Dehydration and hypovolemia

Question 11

nephrogenic diabetes insipidus

Answer 11

-Inability to concentrate urine due to impaired renal tubule response to ADH (vasopressin)
-Leads to excretion of large amounts of dilute urine
-Inherited or secondary to impairment of renal concentration
-Polyuria, dehydration and hypernatremia; good thirst response
-Diagnosis – water deprivation test and/or administration of exogenous ADH
-Treatment - adequate free water intake, thiazide diuretics (proximal tubule reabsorbs water due to sensing dilution), NSAIDs, and a low-salt, low-protein diet

Question 12

diff dx chart of diabetes insipidus

Answer 12

< 1ADH is abnormal -> CDI

Question 13

tests for DI

Answer 13

-All tests for CDI &NDI based on the principle that:
-Increasing the plasma osmolality in normal people – will lead to decreased excretion of urine

-Water deprivation test:
-Simplest
-Most reliable method
-Patient needs constant supervision*
-Serious dehydration may result *

Question 14

water deprivation test

Answer 14

-inpatient- dehydration is dangerous
-Weigh the patient
-Determine electrolyte concentrations, plasma & urinary osmolality
-Voided urine collected hourly; Sp.gr OR osmolality measured

-Dehydration is continued until:
-Orthostatic hypotension
-Postural tachycardia appear
-≥ 5% of the initial body weight has been lost
-OR
-Urinary concentration does not increase > 0.001 sp gr or > 30 mOsm/L in sequentially voided specimens

-Serum electrolytes and osmolality are again determined
-5 units of aqueous vasopressin injected sc.
-Urine for sp gr or osmolality measurement collected one final time 60 min post injection

Question 15

comparing ADH pathology

Answer 15

Question 16

result interpretation

Answer 16

-Normal response produces maximum urine osmolality after dehydration
-often > 1.020 sp gr or > 700 mOsm/L, exceeding the plasma osmolality
-Osmolality does not increase more than an additional 5% after injection of vasopressin

-CDI - generally unable to concentrate urine to greater than the plasma osmolality
-But are able to increase their urine osmolality by > 50% after vasopressin administration

-NDI - unable to concentrate urine to greater than the plasma osmolality and shows no additional response to vasopressin

-Partial CDI- Often able to concentrate urine to above the plasma osmolality -> Show a rise in urine osmolality of > 9% after vasopressin administration

Question 17

ADH measurement

Answer 17

-Measurement of circulating ADH
-Most direct method of diagnosing CDI
-ADH difficult to measure; test not routinely available
-Direct measurement of ADH unnecessary

-Levels of ADH at the end of the water deprivation test (before the vasopressin injection)
-Low in CDI
-Appropriately elevated in NDI

-Water deprivation very accurate
-Plasma ADH levels are diagnostic after either dehydration or infusion of hypertonic saline

Question 18

psychogenic polydipsia

Answer 18

-Difficult problem in differential diagnosis
-Patients may ingest and excrete up to 6 L of fluid/day

-Often emotionally disturbed:
-They usually do not have nocturia
-Nor does their thirst wake them at night
-Life-threatening hyponatremia

-acute psychogenic water drinking- able to concentrate urine during water deprivation

-chronic water intake diminishes medullary tonicity in the kidney
-long standing polydipsia -> unable to concentrate their urine to max levels during water deprivation

-unlike CDI, pts with psychogenic polydipsia show no response to exogenous ADH after water deprivation
After prolonged restriction of fluid intake to ≤ 2 L/day, normal concentrating ability returns within several weeks

Question 19

tx of DI

Answer 19

-Hormone replacement and treatment of any correctable cause
-Permanent renal damage can result

-Desmopressin:
-Synthetic analog of ADH
-Minimal vasoconstrictive properties
-Prolonged antidiuretic activity lasting for 12 to 24 h
-Intranasally, sc, IV, or orally
-Preparation of choice for both adults and children
-A/E – fluid retention; headache; ↑ BP; URI or allergic rhinitis

-Reduction of polyuria
-Nonhormonal drugs- Diuretics, primarily thiazides

-ADH-releasing drugs
-Chlorprpamide (hypoglycemia)
-Carbamazepine
-Clofibrate

-Prostaglandin inhibitors
-Reduce GFR and renal blood flow
-None are effective in NDI [error]

-Thiazides
-Paradoxically reduce urine volume in partial and complete CDI & NDI
-Primarily as a consequence of reducing ECF volume and increasing proximal tubular resorption
-Urine volumes may fall by 25 to 50%
-Restricting salt intake also ↓ urine output by reducing solute load

Question 20

SIADH criteria

Answer 20

-Attributed to excessive ADH release
-Defined as:
-Less than maximally dilute urine in the presence of plasma hypo-osmolality (hyponatremia) WITHOUT:
-Volume depletion or overload
-Emotional stress
-Pain
-Diuretics or other drugs that stimulate ADH secretion,
-AND WITH normal cardiac, hepatic, renal, adrenal, and thyroid function
-dx of exclusion

Question 21

SIADH

Answer 21

-No osmotic or physiologic stimuli are present
-Effects of excess ADH include hypo-osmolality and hyponatremia
-Before the diagnosis of SIADH can be made, both thyroid disease and adrenal insufficiency need to be ruled out
-50% of all diagnosed cases of hyponatremia are due to SIADH
-Acute severe hyponatremia is associated with morbidity and mortality -> Can develop rapidly
-up to 50% all institutionalized geriatric pts show hyponatremia
-up to 70% of cases of hyponatremia are hospital acquired

Question 22

SIADH etiology

Answer 22

-Drugs
-Post-operative stress caused by surgery, use of a mechanical ventilator, or anesthetic agents
-Hormone administration: vasopressin, desmopressin or oxytocin
-CNS disturbances due to infections, stroke (embolic, hemorrhagic), trauma, or neurosurgery
-Pulmonary disorders: pneumonia, tuberculosis emphysema, status asthmaticus, SCLC*

Question 23

disorders associated with SIADH secretion

Answer 23

-Malignancy
-CNS
-Pancreas
-Duodenum
-Lung*
-Lymphoma

-Pulmonary disorders
-Aspergillosis
-Lung abscess
-Pneumonia
-Positive-pressure breathing
-TB

-CNS disorders
-Acute intermittent porphyria
-Acute psychosis
-Brain abscess
-Encephalitis
-Guillain-Barré syndrome

-Head trauma
-Meningitis
-Stroke
-Subdural or subarachnoid hemorrhage

-Endocrine disorders
-Addison’s disease
-Hypopituitarism
-Hypothyroidism

-Miscellaneous causes
-Protein-energy malnutrition
-Surgery

Question 24

symptoms SIADH

Answer 24

-Patient may be asymptomatic, especially when the cause is indolent or subacute. Severe or rapid onset hyponatremia may cause:
-Confusion
-Lethargy
-Vomiting
-Seizures

Question 25

SIADH signs

Answer 25

-Hyponatremia*
-Hypo-osmolality (<275 mosm/kg)*
-Euvolemic-normal volume
-Elevated urinary osmolality (>100 mosm/kg and often at least 300 mosm/kg)
-Normal plasma volume
-Serum uric acid <4 mg/dL
-Normal acid base and potassium balance
-Normal renal function
-Relatively normal creatinine concentration
-Normal adrenal and thyroid function

Question 26

diff dx SIADH

Answer 26

-Hypervolemic hypotonic hyponatremia:
-An increase in total body water and sodium with a decrease in the circulating volume (impaired water excretion)
-Characterized by clinical fluid overload with edema
-CHF, liver cirrhosis with ascites, nephrotic syndrome, protein losing enteropathy

-Hypovolemic hypotonic hyponatremia:
-Characterized by fluid volume loss due to underlying disorder
-Non-renal loss of electrolyte-containing fluid (diuretics, burns, severe diarrhea and vomiting)
-Salt losing renal diseases (interstitial nephritis, obstructive nephropathy)
-Mineralocorticoid deficiencies

Question 27

SIADH management

Answer 27

-Resolution of any CNS symptoms
-Avoid causing CNS complications through too rapid correction of Na+
-Achievement of a safe plasma Na+ level (>120mEq/L)
-Determination and treatment of underlying cause of hypo-osmolality
-Discontinue use of medications which enhance ADH release
-Fluid restriction should be attempted as a first-line therapy ***
-For refractory cases, demeclocycline administration or normal saline infusion -> Tetracycline antibiotic; antagonizes effect of ADH